Neoplasms

All Conditions

Digestive System Diseases

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Wounds and Injuries

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Gastrointestinal Stromal Tumors

Hematoma, Subdural

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Soft Tissue Sarcoma

All Drugs and Chemicals

Mitogens

Patients receive rogaratinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and CT, MRI, and PET-CT every 8 weeks. Patients may also undergo blood sample collection on study.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Rogaratinib

Suzanne George

This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To estimate the objective radiographic response rate to single agent rogaratinib (BAY 1163877) in two cohorts of patients with sarcoma: Cohort A defined as patients with a sarcoma which harbors an alteration in fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4 identified by next-generation sequencing profiling, and Cohort B defined as patients with advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST).

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) in patients in Cohort A and Cohort B treated with rogaratinib (BAY 1163877).

II. Further assessment for safety and tolerability.

EXPLORATORY OBJECTIVES:

I. To evaluate serial measurements of FGFR and FGFR ligand in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing (RNA-seq) (pre-treatment biopsy and post-progression biopsy \[if available\]).

II. Whole exome sequencing (WES) of the pre-treatment biopsy and post-progression biopsy (if available) to help identify mechanisms of resistance.

III. To bank tumor material, germline deoxyribonucleic acid (DNA), and peripheral blood for potential future research for participating subjects who provide additional consent.

IV. To explore rogaratinib exposure with pharmacodynamics effects (i.e., clinical response, toxicity, and markers of FGFR pathway inhibition).

OUTLINE:

Patients receive rogaratinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT every 8 weeks. Patients may also undergo blood sample collection on study.

After completion of study treatment, patients are followed up at 30 days.

Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)

Phase 2 Study of Rogaratinib (BAY 1163877) in the Treatment of Patients With Sarcoma Harboring Alterations in Fibroblast Growth Factor Receptor (FGFR) 1-4 and SDH-Deficient Gastrointestinal Stromal Tumor (GIST)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will be evaluated in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing. Estimation of continuous biomarker measures will be via mean or median as appropriate and standard deviation.

Will identify mechanisms of resistance via whole exome sequencing of pre- and post-treatment biopsies and considered exploratory.

The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Will be estimated using Kaplan-Meier method.

Adverse events will be measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Spots Global Cancer Trial Database for stage iv gastric and omental gastrointestinal stromal tumor ajcc v8